Biopolym. Cell. 2016; 32(2):111-117.
http://dx.doi.org/10.7124/bc.000913
Structure and Function of Biopolymers
Uncoupling of oxidative phosphorylation and antioxidants affect fusion of primary human myoblasts in vitro
1, 2, 3Zakharova V. V., 3Dib C., 3Saada Y. B., 1, 3Vassetzky Y. S., 1Galkin I. I., 1Chernyak B. V., 1Popova E. N.
  1. A. N. Belozersky Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University
    Vorobyevy gory, house 1, building 40, Moscow, Russian Federation, 119992
  2. Faculty of Bioengineering and Bioinformatics, M. V. Lomonosov Moscow State University
    Vorobyevy gory, house 1, building 40, Moscow, Russian Federation, 119992
  3. CNRS UMR 8126, Universit Paris-Sud 11, Institut Gustave Roussy
    114, rue Edouard Vaillant, Villejuif, France, 94805

Abstract

Reactive oxygen species are at the origin of muscular fatigue and atrophy. They are also linked to muscular dystrophies, a group of human genetic diseases. Several studies point to the benefits of application of antioxidants and uncouplers of oxidative phosphorylation to improve the functional activity of normal and pathological muscles. Other studies point to potential dangers of these compounds. Aim. To study the effect of mitochondria-targeted antioxidants and uncouplers of oxidative phosphorylation on muscle differentiation. Methods. Muscle differentiation was induced by serum starvation and monitored by troponin T staining. Results. the mitochondria-targeted uncoupler of oxidative phosphorylation C12TPP, but not the mitochondria-targeted antioxidant SkQ1, inhibit fusion of primary myoblasts upon their differentiation, but do not affect the synthesis of troponin T, a protein marker of muscle differentiation. Conclusion. The effect of C12TPP could be at least partially mediated by inhibition of reactive oxygen species (ROS) production since antioxidant N-acetylcysteine at high doses also inhibited differentiation of myoblasts.
Keywords: skeletal muscle, muscle differentiation, mitochondria-targeted antioxidants, uncouplers of oxidative phosphorylation
Full text: (PDF, in English)

References

[1] Powers SK, Smuder AJ, Judge AR. Oxidative stress and disuse muscle atrophy: cause or consequence? Curr Opin Clin Nutr Metab Care. 2012;15(3):240-5.
[2] Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44-84.
[3] Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417(1):1-13.
[4] Messina S, Altavilla D, Aguennouz M, Seminara P, Minutoli L, Monici MC, Bitto A, Mazzeo A, Marini H, Squadrito F, Vita G. Lipid peroxidation inhibition blunts nuclear factor-kappaB activation, reduces skeletal muscle degeneration, and enhances muscle function in mdx mice. Am J Pathol. 2006;168(3):918-26.
[5] Bosnakovski D, Xu Z, Gang EJ, Galindo CL, Liu M, Simsek T, Garner HR, Agha-Mohammadi S, Tassin A, Coppée F, Belayew A, Perlingeiro RR, Kyba M. An isogenetic myoblast expression screen identifies DUX4-mediated FSHD-associated molecular pathologies. EMBO J. 2008;27(20):2766-79.
[6] Turki A, Hayot M, Carnac G, Pillard F, Passerieux E, Bommart S, Raynaud de Mauverger E, Hugon G, Pincemail J, Pietri S, Lambert K, Belayew A, Vassetzky Y, Juntas Morales R, Mercier J, Laoudj-Chenivesse D. Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction. Free Radic Biol Med. 2012;53(5):1068-79.
[7] Passerieux E, Hayot M, Jaussent A, Carnac G, Gouzi F, Pillard F, Picot MC, Böcker K, Hugon G, Pincemail J, Defraigne JO, Verrips T, Mercier J, Laoudj-Chenivesse D. Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: a double-blind randomized controlled clinical trial. Free Radic Biol Med. 2015;81:158-69.
[8] Canton M, Menazza S, Di Lisa F. Oxidative stress in muscular dystrophy: from generic evidence to specific sources and targets. J Muscle Res Cell Motil. 2014;35(1):23-36.
[9] Ardite E, Barbera JA, Roca J, Fernández-Checa JC. Glutathione depletion impairs myogenic differentiation of murine skeletal muscle C2C12 cells through sustained NF-kappaB activation. Am J Pathol. 2004;165(3):719–28.
[10] Whitehead NP, Yeung EW, Froehner SC, Allen DG. Skeletal muscle NADPH oxidase is increased and triggers stretch-induced damage in the mdx mouse. PLoS One. 2010;5(12):e15354.
[11] Lee KH, Kim DG, Shin NY, Song WK, Kwon H, Chung CH, Kang MS. NF-kappaB-dependent expression of nitric oxide synthase is required for membrane fusion of chick embryonic myoblasts. Biochem J. 1997;324 ( Pt 1):237-42.
[12] Lee S, Tak E, Lee J, Rashid MA, Murphy MP, Ha J, Kim SS. Mitochondrial H2O2 generated from electron transport chain complex I stimulates muscle differentiation. Cell Res. 2011;21(5):817-34.
[13] Koren A, Sauber C, Sentjurc M, Schara M. Free radicals in tetanic activity of isolated skeletal muscle. Comp Biochem Physiol B. 1983;74(3):633-5.
[14] Jackson MJ, Pye D, Palomero J. The production of reactive oxygen and nitrogen species by skeletal muscle. J Appl Physiol (1985). 2007;102(4):1664-70.
[15] Langen RC, Van Der Velden JL, Schols AM, Kelders MC, Wouters EF, Janssen-Heininger YM. Tumor necrosis factor-alpha inhibits myogenic differentiation through MyoD protein destabilization. FASEB J. 2004;18(2):227–37.
[16] Sheu SS, Nauduri D, Anders MW. Targeting antioxidants to mitochondria: a new therapeutic direction. Biochim Biophys Acta. 2006;1762(2):256-65.
[17] Mistry Y, Poolman T, Williams B, Herbert KE. A role for mitochondrial oxidants in stress-induced premature senescence of human vascular smooth muscle cells. Redox Biol. 2013;1:411-7.
[18] Talbert EE, Smuder AJ, Min K, Kwon OS, Szeto HH, Powers SK. Immobilization-induced activation of key proteolytic systems in skeletal muscles is prevented by a mitochondria-targeted antioxidant. J Appl Physiol (1985). 2013;115(4):529–38.
[19] Siegel MP, Kruse SE, Percival JM, Goh J, White CC, Hopkins HC, Kavanagh TJ, Szeto HH, Rabinovitch PS, Marcinek DJ. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell. 2013;12(5):763-71.
[20] Cunha FM, Caldeira da Silva CC, Cerqueira FM, Kowaltowski AJ. Mild mitochondrial uncoupling as a therapeutic strategy. Curr Drug Targets. 2011;12(6):783-9.
[21] Caldeira da Silva CC, Cerqueira FM, Barbosa LF, Medeiros MH, Kowaltowski AJ. Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity. Aging Cell. 2008;7(4):552–60.
[22] Dupuis L, Gonzalez de Aguilar JL, Echaniz-Laguna A, Eschbach J, Rene F, Oudart H, Halter B, Huze C, Schaeffer L, Bouillaud F, Loeffler JP. Muscle mitochondrial uncoupling dismantles neuromuscular junction and triggers distal degeneration of motor neurons. PLoS One. 2009;4(4):e5390.
[23] Severin FF, Severina II, Antonenko YN, Rokitskaya TI, Cherepanov DA, Mokhova EN, Vyssokikh MY, Pustovidko AV, Markova OV, Yaguzhinsky LS, Korshunova GA, Sumbatyan NV, Skulachev MV, Skulachev VP. Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore. Proc Natl Acad Sci U S A. 2010;107(2):663-8.
[24] Antonenko YN, Avetisyan AV, Cherepanov DA, Knorre DA, Korshunova GA, Markova OV, Ojovan SM, Perevoshchikova IV, Pustovidko AV, Rokitskaya TI, Severina II, Simonyan RA, Smirnova EA, Sobko AA, Sumbatyan NV, Severin FF, Skulachev VP. Derivatives of rhodamine 19 as mild mitochondria-targeted cationic uncouplers. J Biol Chem. 2011;286(20):17831-40.
[25] Plotnikov EY, Silachev DN, Jankauskas SS, Rokitskaya TI, Chupyrkina AA, Pevzner IB, Zorova LD, Isaev NK, Antonenko YN, Skulachev VP, Zorov DB. Mild uncoupling of respiration and phosphorylation as a mechanism providing nephro- and neuroprotective effects of penetrating cations of the SkQ family. Biochemistry (Mosc). 2012;77(9):1029-37.
[26] Khailova LS, Silachev DN, Rokitskaya TI, Avetisyan AV, Lyamsaev KG, Severina II, Il’yasova TM, Gulyaev MV, Dedukhova VI, Trendeleva TA, Plotnikov EY, Zvyagilskaya RA, Chernyak BV, Zorov DB, Antonenko YN, Skulachev VP. A short-chain alkyl derivative of Rhodamine 19 acts as a mild uncoupler of mitochondria and a neuroprotector. Biochim Biophys Acta. 2014;1837(10):1739–47.
[27] Barro M, Carnac G, Flavier S, Mercier J, Vassetzky Y, Laoudj-Chenivesse D. Myoblasts from affected and non-affected FSHD muscles exhibit morphological differentiation defects. J Cell Mol Med. 2010;14(1-2):275-89.
[28] Dib C, Bou Saada Y, Dmitriev P, Richon C, Dessen P, Laoudj-Chenivesse D, Carnac G, Lipinski M, Vassetzky YS. Correction of the FSHD myoblast differentiation defect by fusion with healthy myoblasts. J Cell Physiol. 2016;231(1):62-71.
[29] Buggisch M, Ateghang B, Ruhe C, Strobel C, Lange S, Wartenberg M, Sauer H. Stimulation of ES-cell-derived cardiomyogenesis and neonatal cardiac cell proliferation by reactive oxygen species and NADPH oxidase. J Cell Sci. 2007;120(Pt 5):885-94.
[30] Dmitriev P, Barat A, Polesskaya A, O’Connell MJ, Robert T, Dessen P, Walsh TA, Lazar V, Turki A, Carnac G, Laoudj-Chenivesse D, Lipinski M, Vassetzky YS. Simultaneous miRN-A and mRNA transcriptome profiling of human myoblasts reveals a novel set of myogenic differentiation-associated miRNAs and their target genes. BMC Genomics. 2013;14:265.
[31] Antonenko YN, Avetisyan AV, Bakeeva LE, Chernyak BV, Chertkov VA, Domnina LV, Ivanova OY, Izyumov DS, Khailova LS, Klishin SS, Korshunova GA, Lyamzaev KG, Muntyan MS, Nepryakhina OK, Pashkovskaya AA, Pletjushkina OY, Pustovidko AV, Roginsky VA, Rokitskaya TI, Ruuge EK, Saprunova VB, Severina II, Simonyan RA, Skulachev IV, Skulachev MV, Sumbatyan NV, Sviryaeva IV, Tashlitsky VN, Vassiliev JM, Vyssokikh MY, Yaguzhinsky LS, Zamyatnin AA Jr, Skulachev VP. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies. Biochemistry (Mosc). 2008;73(12):1273-87.
[32] Apostolova N, Victor VM. Molecular strategies for targeting antioxidants to mitochondria: therapeutic implications. Antioxid Redox Signal. 2015;22(8):686-729.
[33] Williamson DL, Butler DC, Alway SE. AMPK inhibits myoblast differentiation through a PGC-1alpha-dependent mechanism. Am J Physiol Endocrinol Metab. 2009;297(2):E304-14.